This application for a Senior Scientist Award (K05) is based upon research grants currently funded by NIDA and NIAAA. I am Principal Investigator for a NIDA RO1 research grant Psychostimulant Abuse: Novel Treatment Approaches (DA10757). I also serve as Principal Investigator for a NIDA Drug Abuse Research Training Program (DA07252). I serve as a Scientific Director for a NIDA P50 research center grant Polydrug Abuse in Women (DA04059). I also serve as Principal Investigator for a NIAAA R01 research grant Brain Alcohol MRS and Family History of Alcoholism (AA11618). I continue to serve as Co-Investigator for a NIDA SPIRCAP project New Strategies for Anti-Cocaine Medications (DA11007). The research protocol described in this competing renewal grant application for a Research Scientist Award (RSA DA00064) highlights assessment of the safety and effectiveness of new medications for the treatment of cocaine and concurrent cocaine- alcohol abuse. New medications are proposed for Phase 1 and Phase 2 clinical investigations. Treatment medications will be evaluated in men and women during residence on a dedicated clinical research ward. Women will be studied during two phases of the menstrual cycle (mid-follicular and mid-luteal) to determine if hormonal changes across the menstrual cycle influence the effects of treatment medications. Subjective effects of drug induced euphoria/dysphoria and drug craving will be examined with standard computerized measures before and after challenge dose administration. Medication and abused drug effects on neuroendocrine and neuroimmune function will be evaluated to provide another index of medication safety, and to identify possible biologic mechanisms of medication action. Medication and placebo effects on the pharmacokinetics of cocaine and cocaethylene will be examined. Medication effects will also be evaluated with magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). Proposed plans for professional growth include studies of neuroendocrinology, magnetic resonance imaging, magnetic resonance angiography and immunology.